Synthesis and reactions of quinones with some possible biological applications

Abstract

The regioselective syntheses of various 5-acetoxy-2,3-disubstituted-1,4-naphthoquinone derivatives from 5-acetoxy-2-bromo-1,4-naphthoquinone with yields ranging from 80-90% have been performed by modifying the Jacobsen-Thorssell oxidative substitution.

Interest in these types of quinones is emerging in several different fields. since naphthoquinone derivatives have been shown to inhibit the HIV-1 reverse transcriptase (RT), some of the disubstituted naphthoquinones prepared in this work were synthesized to explore the nature of the quinone binding site on RT. Some of the compounds show interesting levels of anti-RT activity with 5-hydroxy-3-methyl-1,4-naphthoquinone being the most potent of the compounds studied.

A synthetic approach to the benzo[b]fluorene ring system of the kinamycins and related natural products, based on such a dialkylation sequence is proposed. Model studies concerning the stereoselective oxidative elaboration of the D-ring of the kinamuycins and the regioselective introduction of the diazo group are described. Preliminary model studies concerning the construction of the A ring of the benzo[b]fluorene natural product cysfluoretin are also reported.